We propose to continue our study of the roles played by anesthetics themselves, separated from their resultant hemodynamic effects, upon occurrence, extent, and consequences of vital organ ischemia. Our primary interest is myocardial ischemia, because patients with coronary artery disease, often of undetermined extent, frequently udergo anesthesia and surgery. In addition, we and others have developed evidence that the controllable depressant attributes of anesthetics may favorably redistribute myocardial blood flow and decrease oxygen demand, and thus be useful as treatment for myocardial ischemia. We originated the concept that anesthetics should be compared in equi-cerebral depressant dosages as usual, but at equal external cardiac workloads as well. This permits intrinsic drug effects on contractility and blood flow distribution to be separated from effects on the heart of anesthetic-related resultant hemodynamics. Our swine model fixes external workloads, measures myocardial VO2; then we calculate cardiac energy efficiency. We have shown efficiency to be substantially different at equal workloads and heart rates between anesthetics. Next, we propose to study efficiency in presence of critical coronary stenoses and use graded workload increments to study which anesthetic produced the best protection in this clinically relevant situation. We can also measure regional arterial inflow-venous outflow, and have originated a dynamic model of coronary vascular recruitment during graded inflow reductions. We wish to compare anesthetics with respect to which permits best recruitment, despite equal external hemodynamics. Beta and/or calcium entry blockers will be added to the anesthetics to determine if further protection is provided. We also plan to continue our series of studies of cardiac risk in patients, by retrospective studies of effects of invasive monitoring, beta blockade, heart rate changes, and obesity, on incidence and severity of perioperative myocardial infarction. FInally, we propose to study post-thoracotomy ECG changes,to better characterize them with respect to detection of myocardial ischemia